Skip to main content
Log in

Biofilm Formation by Cryptococcus neoformans Under Distinct Environmental Conditions

  • Published:
Mycopathologia Aims and scope Submit manuscript

Abstract

Cryptococcus neoformans is an opportunistic fungal pathogen with a propensity to infect the central nervous system of immune compromised individuals causing life-threatening meningoencephalitis. Cryptococcal biofilms have been described as a protective niche against microbial predators in nature and shown to enhance resistance against antifungal agents and specific mediators of host immune responses. Based on the potential importance of cryptococcal biofilms to its survival in the human host and in nature, these studies were designed to investigate those factors that mediate biofilm formation by C. neoformans. We observed that C. neoformans preferentially grew as planktonic cells when cultured under specific conditions designed to mimic growth within host tissues (37°C, neutral pH, and ~5% CO2) or phagocytes (37°C, acidic pH, and ~5% CO2) and as biofilms when cultured under conditions such as those encountered in the external environment (25–37°C, neutral pH, and ambient CO2). Altogether, our studies suggest that conditions similar to those observed in its natural habitat may be conducive to biofilm formation by C. neoformans.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Mitchell TG, Perfect JR. Cryptococcosis in the era of AIDS–100 years after the discovery of Cryptococcus neoformans. Clin Microbiol Rev. 1995;8(4):515–48.

    PubMed  CAS  Google Scholar 

  2. Kidd SE, Chow Y, Mak S, Bach PJ, Chen H, Hingston AO, et al. Characterization of environmental sources of the human and animal pathogen Cryptococcus gattii in British Columbia, Canada, and the Pacific Northwest of the United States. Appl Environ Microbiol. 2007;73(5):1433–43. doi:10.1128/AEM.01330-06.

    Article  PubMed  CAS  Google Scholar 

  3. Steenbergen JN, Nosanchuk JD, Malliaris SD, Casadevall A. Cryptococcus neoformans virulence is enhanced after growth in the genetically malleable host Dictyostelium discoideum. Infect Immun. 2003;71(9):4862–72. doi:10.1128/IAI.71.9.4862-4872.2003.

    Article  PubMed  CAS  Google Scholar 

  4. Steenbergen JN, Shuman HA, Casadevall A. Cryptococcus neoformans interactions with amoebae suggest an explanation for its virulence and intracellular pathogenic strategy in macrophages. Proc Natl Acad Sci USA. 2001;98(26):15245–50. doi:10.1073/pnas.261418798.

    Article  PubMed  CAS  Google Scholar 

  5. Casadevall A, Steenbergen JN, Nosanchuk JD. ‘Ready made’ virulence and ‘dual use’ virulence factors in pathogenic environmental fungi—the Cryptococcus neoformans paradigm. Curr Opin Microbiol. 2003;6(4):332–7. doi:10.1016/S1369-5274(03)00082-1.

    Article  PubMed  Google Scholar 

  6. Hall-Stoodley L, Costerton JW, Stoodley P. Bacterial biofilms: from the natural environment to infectious diseases. Nat Rev Microbiol. 2004;2(2):95–108. doi:10.1038/nrmicro821.

    Article  PubMed  CAS  Google Scholar 

  7. Joubert LM, Wolfaardt GM, Botha A. Microbial exopolymers link predator and prey in a model yeast biofilm system. Microb Ecol. 2006;52(2):187–97. doi:10.1007/s00248-006-9063-7.

    Article  PubMed  Google Scholar 

  8. Martinez LR, Casadevall A. Susceptibility of Cryptococcus neoformans biofilms to antifungal agents in vitro. Antimicrob Agents Chemother. 2006;50(3):1021–33. doi:10.1128/AAC.50.3.1021-1033.2006.

    Article  PubMed  CAS  Google Scholar 

  9. Martinez LR, Casadevall A. Cryptococcus neoformans cells in biofilms are less susceptible than planktonic cells to antimicrobial molecules produced by the innate immune system. Infect Immun. 2006;74(11):6118–23. doi:10.1128/IAI.00995-06.

    Article  PubMed  CAS  Google Scholar 

  10. Walsh TJ, Schlegel R, Moody MM, Costerton JW, Salcman M. Ventriculoatrial shunt infection due to Cryptococcus neoformans: an ultrastructural and quantitative microbiological study. Neurosurgery. 1986;18(3):373–5. doi:10.1097/00006123-198603000-00025.

    Article  PubMed  CAS  Google Scholar 

  11. Banerjee U, Gupta K, Venugopal P. A case of prosthetic valve endocarditis caused by Cryptococcus neoformans var. neoformans. J Med Vet Mycol. 1997;35(2):139–41. doi:10.1080/02681219780001031.

    Article  PubMed  CAS  Google Scholar 

  12. Braun DK, Janssen DA, Marcus JR, Kauffman CA. Cryptococcal infection of a prosthetic dialysis fistula. Am J Kidney Dis. 1994;24(5):864–7.

    PubMed  CAS  Google Scholar 

  13. Penk A, Pittrow L. Role of fluconazole in the long-term suppressive therapy of fungal infections in patients with artificial implants. Mycoses. 1999;42(Suppl 2):91–6.

    PubMed  CAS  Google Scholar 

  14. Martinez LR, Christaki E, Casadevall A. Specific antibody to Cryptococcus neoformans glucurunoxylomannan antagonizes antifungal drug action against cryptococcal biofilms in vitro. J Infect Dis. 2006;194(2):261–6. doi:10.1086/504722.

    Article  PubMed  CAS  Google Scholar 

  15. Martinez LR, Casadevall A. Cryptococcus neoformans biofilm formation depends on surface support and carbon source and reduces fungal cell susceptibility to heat, cold, and UV light. Appl Environ Microbiol. 2007;73(14):4592–601. doi:10.1128/AEM.02506-06.

    Article  PubMed  CAS  Google Scholar 

  16. Peeters E, Nelis HJ, Coenye T. Comparison of multiple methods for quantification of microbial biofilms grown in microtiter plates. J Microbiol Methods. 2008;72(2):157–65. doi:10.1016/j.mimet.2007.11.010.

    Article  PubMed  CAS  Google Scholar 

  17. Martinez LR, Casadevall A. Specific antibody can prevent fungal biofilm formation and this effect correlates with protective efficacy. Infect Immun. 2005;73(10):6350–62. doi:10.1128/IAI.73.10.6350-6362.2005.

    Article  PubMed  CAS  Google Scholar 

  18. Matz C, McDougald D, Moreno AM, Yung PY, Yildiz FH, Kjelleberg S. Biofilm formation and phenotypic variation enhance predation-driven persistence of Vibrio cholerae. Proc Natl Acad Sci USA. 2005;102(46):16819–24. doi:10.1073/pnas.0505350102.

    Article  PubMed  CAS  Google Scholar 

  19. Matz C, Kjelleberg S. Off the hook—how bacteria survive protozoan grazing. Trends Microbiol. 2005;13(7):302–7. doi:10.1016/j.tim.2005.05.009.

    Article  PubMed  CAS  Google Scholar 

  20. Begun J, Gaiani JM, Rohde H, Mack D, Calderwood SB, Ausubel FM, et al. Staphylococcal biofilm exopolysaccharide protects against Caenorhabditis elegans immune defenses. PLoS Pathog. 2007;3(4):e57. doi:10.1371/journal.ppat.0030057.

    Article  PubMed  Google Scholar 

  21. Mitchell AP. Fungal CO2 sensing: a breath of fresh air. Curr Biol. 2005;15(22):R934–6. doi:10.1016/j.cub.2005.10.064.

    Article  PubMed  CAS  Google Scholar 

  22. Rittershaus PC, Kechichian TB, Allegood JC, Merrill AH Jr, Hennig M, Luberto C, et al. Glucosylceramide synthase is an essential regulator of pathogenicity of Cryptococcus neoformans. J Clin Invest. 2006;116(6):1651–9. doi:10.1172/JCI27890.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We will like to thank Jose Lopez-Ribot Pharm.D., Ph.D. for critical reading of the manuscript. This work was supported by grants RO1 AI071752–03 and 5G12RR013646–09 from the National Institutes of Allergy and Infectious Diseases (NIAID) and the National Center for Research Resources (NCRR), respectively, of the National Institutes of Health (NIH). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIAID, NCRR, or the National Institutes of Health.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Floyd L. Wormley Jr..

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ravi, S., Pierce, C., Witt, C. et al. Biofilm Formation by Cryptococcus neoformans Under Distinct Environmental Conditions. Mycopathologia 167, 307–314 (2009). https://doi.org/10.1007/s11046-008-9180-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11046-008-9180-6

Keywords

Navigation